Aphasia after stroke is associated with high mortality and severe motor, social, and cognitive disability. During the past decade, therapies administered by stroke teams have made great strides to limit the damage due to a stroke. Progress in aphasia rehabilitation has not experienced the same rapid advancement. This proposal is based on evidence from children and adults provided by us and others suggesting that the brain may have untapped potential for recovery of aphasia after stroke. The first step toward accessing that potential and the overall aim of this proposal is to understand how the neural circuitry supporting language functions responds to acute ischemic injury in order to restore language functions. Further, we will take the next step of testing the impact of a new therapeutic strategy on aphasia recovery and on the plasticity of the underlying neural circuitry of language. By administering an intervention, we will provide clinical and neuroimaging evidence that constraint-induced aphasia therapy (CIAT) positively affects language recovery after stroke. The findings will have implications for understanding of the differences in language plasticity between different age groups and for the design of effective treatment interventions. To fill the gap in our knowledge we propose a study with the following specific aims: (1) In young and old adults we will map longitudinal changes in language activation patterns and determine language localization and lateralization using fMRI after LMCA stroke. We will compare the language activation patterns between the groups of adults with those found in children with perinatal and postnatal stroke from our previous studies; (2) In dextral and non-dextral LMCA stroke patients, we will map changes in language activation using fMRI, assess the differences in post-stroke language recovery between these groups, and determine whether non- dextral patients exhibit a) more symmetric or right-lateralized language distribution as compared to dextral patients, b) whether the changes in lateralization correlate with recovery from aphasia, and c) whether these patients activate additional language processing and production areas; and (3) We will demonstrate via a pilot study that CIAT administered 1 year after the incident stroke positively influences recovery of chronic aphasia after stroke when compared to traditional care. We will apply CIAT and use fMRI and neuropsychological measures to document the relationship between the clinical and anatomical correlates of post-stroke language recovery in dextral and non-dextral LMCA stroke patients. PUBLIC HEALTH RELEVANCE: Project narrative Loss of language functions after stroke (aphasia) is one of the most feared symptoms of stroke. Language is a fundamentally human cognitive function. Without it, our social and economic status in society is tremendously impaired. Highly productive members of the society who lose language capability due to a stroke are often devastated and may not be able to re-enter social and professional life at the pre-stroke level. In this study we will examine the changes the brain undergoes while recovering from an aphasia-causing stroke, the mechanisms that underlie such recovery, and test the efficacy of a new and promising method of aphasia rehabilitation called constraint-induced aphasia therapy.